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Heterozygous deletion of Seipin in islet beta cells of male mice has an impact on insulin synthesis and secretion through reduced PPARγ expression

  • Jianwei Xiong
  • Peng Sun
  • Ya Wang
  • Xu Hua
  • Wenyu Song
  • Yan Wang
  • Jie Wu
  • Wenfeng YuEmail author
  • George LiuEmail author
  • Ling ChenEmail author



Berardinelli–Seip congenital lipodystrophy type 2 (BSCL2) is an autosomal recessive disorder characterised by lipodystrophy and insulin resistance. BSCL2 is caused by loss-of-function mutations in the Seipin gene (also known as Bscl2). Deletion of this gene in mice induces insulin resistance, glucose intolerance and a loss of adipose tissue. This study evaluated the effects of genetic deletion of Seipin on islet beta cell function.


We examined seipin expression in islet cells and measured glucose profiles, insulin synthesis, glucose-stimulated insulin secretion (GSIS), islet expression of peroxisome proliferator-activated receptor γ (PPARγ), levels of Pdx-1, Nkx6.1, Glut2 (also known as Slc2a2) and proinsulin mRNA, nuclear translocation of pancreatic duodenal homeobox 1 (PDX-1), islet numbers, and beta cell mass and proliferation in male and female Seipin-knockout homozygous (Seipin−/−) and heterozygous (Seipin+/−) mice.


Male and female Seipin−/− mice displayed glucose intolerance, insulin resistance, hyperinsulinaemia and a lack of adipose tissue. By contrast, male but not female Seipin+/− mice showed glucose intolerance without adipose tissue loss or insulin resistance. Seipin was highly expressed in islet beta cells in wild-type mice. Expression of islet PPARγ was reduced in male Seipin−/− and Seipin+/− mice but not in female Seipin−/− or Seipin+/− mice. Treatment of male Seipin+/− mice with rosiglitazone corrected the glucose intolerance. Male Seipin+/− mice displayed a decrease in islet insulin concentration and GSIS with low expression of Pdx-1, Nkx6.1, Glut2 and proinsulin, and a decline in PDX-1 nuclear translocation; these changes were rescued by rosiglitazone administration. Male Seipin−/− mice showed obvious, but rosiglitazone-sensitive, increases in islet insulin concentration, islet number and beta cell mass and proliferation, with a notable decline in GSIS. Ovariectomised female Seipin+/− mice displayed glucose intolerance and deficits in insulin synthesis and secretion, with a decline in islet PPARγ level; these deleterious effects were reversed by administration of oestradiol or rosiglitazone.


Heterozygous deletion of Seipin in islet beta cells impacts on insulin synthesis and secretion through reduced PPARγ expression. This leads to glucose intolerance and is relieved by oestradiol, which rescues PPARγ expression.


Berardinelli Islet beta cell Oestrogen Peroxisome proliferator-activated receptor γ (PPARγ) Seip congenital lipodystrophy type 2 (BSCL2) Seipin 



Berardinelli–Seip congenital lipodystrophy type 2


Endoplasmic reticulum


Glucose-stimulated insulin secretion


Pancreatic duodenal homeobox 1


Peroxisome proliferator-activated receptor γ


Peroxisome proliferator-activated receptor γ response element


Reverse-transcription quantitative PCR




Contribution statement

JX, PS, YaW, XH, WS and YanW contributed to acquisition, analysis and interpretation of data. PS and LC wrote the draft of the manuscript. JW, GL, WY and LC contributed to the conception and design of this work. All authors revised the manuscript critically for important intellectual content and approved the final version to be published. LC is the guarantor of this work.


This work was supported by the National Natural Science Foundation of China (81471157; 81671253; 81603169), National 973 Basic Research Program of China (2014CB943303), Jiangsu provincial Natural Science Foundation of China (BE2016765; BK20161027) and Natural Science Research Program for Higher Education in Jiangsu Province (16KJB310007).

Duality of interest

The authors declare that there is no duality of interest associated with this manuscript.

Supplementary material

125_2019_5038_MOESM1_ESM.pdf (312 kb)
ESM (PDF 312 kb)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.State Key Laboratory of Reproductive MedicineNanjing Medical UniversityNanjingChina
  2. 2.Department of Obstetrics and Gynecology, The First Affiliated Hospital of Nanjing Medical UniversityNanjing Medical UniversityNanjingChina
  3. 3.Key Laboratory of Human Functional Genomics of Jiangsu Province, Department of Biochemistry and Molecular BiologyNanjing Medical UniversityNanjingChina
  4. 4.Department of PhysiologyNanjing Medical UniversityNanjingChina
  5. 5.Key Laboratory of Medical Molecular BiologyGuizhou Medical UniversityGuiyangChina
  6. 6.Institute of Cardiovascular Sciences, Peking University and Key Laboratory of Cardiovascular Sciences, China Administration of EducationBeijingChina

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